Immune-Mediated Necrotizing Myopathy, Multiple Sclerosis (MS), Myasthenia Gravis (MG), Neuromyelitis Optica Spectrum Disorder, Systemic Lupus Erythematosus, Systemic Sclerosis
Conditions
Keywords
CD20/BCMA-directed CAR-T cells
Brief summary
This is an investigator-initiated, single-center, open-label study of C-CAR168, an autologous bi-specific CAR-T therapy targeting CD20 and BCMA, for the treatment of adult patients with autoimmune diseases refractory to standard therapy
Interventions
BIOLOGICALCD20/BCMA-directed CAR-T cells Autologous 2nd generation
CD20/BCMA-directed CAR-T cells, single infusion intravenously
Sponsors
The Affiliated Hospital of Qingdao University
Shanghai AbelZeta Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 70 years old at the time of signing the Informed Consent Form (ICF). * Diagnosed as Multiple sclerosis (MS)/Neuromyelitis Optica Spectrum Disorders (NMOSD)/Myasthenia Gravis (MG)/Systemic Lupus Erythematosus (SLE)/ Systemic Sclerosis (SSc)/ Immune-Mediated Necrotizing Myopathy (IMNM) according to recognized diagnostic criteria for at least 6 months. * Prior treatment failure with standard therapy. * Adequate bone marrow, coagulation, cardiopulmonary, liver and renal function.
Exclusion criteria
* Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Treponema Pallidum (TP) positive, Cytomegalovirus (CMV) DNA positive, Epstein-Barr Virus (EBV) DNA positive. * Uncontrolled active infection. * Live vaccine injection within 4 weeks prior to signing the ICF. * Major organ transplantation history or bone marrow/hematopoietic stem cell transplantation history. * Severe cardiovascular diseases within the past 6 months prior to screening. * A history of ≥ Grade 2 bleeding within 4 weeks prior to screening, or requiring long-term anticoagulants treatment. * Inadequate washing time for previous treatment. * Previously treated with CAR-T cell products or genetically modified T cell therapies. * Pregnant or lactating women. * Severe central nervous system diseases or pathological changes. * Malignancy history within 5 years prior to signing the ICF. * Any contraindication to lumbar puncture for MS or NMOSD.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of Adverse Events [Safety and Tolerability] | Throughout the first 3 months follow up period completion | Incidence and severity of adverse events (AE) and serious adverse events (SAE) within three months following infusion |
| The subsequent recommended dose of C-CAR168 in patients with autoimmune diseases refractory to standard therapy | Throughout the first 24 months follow up period completion | Based on the assessment of overall safety profile |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events (AE) | Throughout the first 24 months follow up period completion | Incidence and severity of adverse events (AE) and serious adverse events (SAE) during the study |
| MS: No Evidence of Disease Activity-3 (NEDA-3) | Throughout the first 24 months follow up period completion | Proportion of participants achieving NEDA-3 at 6 months post-infusion and during the study period |
| MS and NMOSD: Expanded Disability Status Scale (EDSS) | Throughout the first 24 months follow up period completion | Change from baseline in EDSS at 6 months and 24 months post-infusion. EDSS and its associated functional system(FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death). |
| MS and NMOSD: MRI | Throughout the first 24 months follow up period completion | Number of T1 gadolinium-enhancing lesions and new or enlarging T2 lesions, as well as their change from baseline,at 6 months and 24 months post-infusion. Change from baseline in total T2 lesion volume, gray matter volume (GMV),white matter volume (WMV), and brain volume (BV), as well as annualized-brain volume loss (a-BVL), at 6 months and 24 months post-infusion |
| MS and NMOSD: Annualized Relapse Rate (ARR) | Throughout the first 24 months follow up period completion | ARR at 6 months and 24 months post-infusion |
| MG: Minimal Symptom Expression (MSE) and Minimal Clinically Important Difference (MCID) | Throughout the first 24 months follow up period completion | Proportion of participants achieving MSE or MCID at 6 months and 24 months post-infusion |
| MG: Quantitative Myasthenia Gravis Score (QMGS) | Throughout the first 24 months follow up period completion | Change from baseline in QMGS at 6 months and 24 months post-infusion. The Quantitative Myasthenia Gravis Score (QMGS) has a score range from 0 to 39, and higher scores indicate a worse clinical outcome. |
| MG: Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale | Throughout the first 24 months follow up period completion | Change from baseline in MG-ADL at 6 months and 24 months post-infusion. The Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale has a score range from 0 to 24, and higher scores indicate a worse clinical outcome. |
| SLE: Definition Of Remission In SLE (DORIS), Lupus Low Disease Activity State (LLDAS), Systemic Lupus Erythematosus Responder Index-4 (SRI-4) | Throughout the first 24 months follow up period completion | Proportion of participants achieving DORIS or LLDAS or SRI-4 at 6 months post-infusion and during the study period |
| SLE: Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K), | Throughout the first 24 months follow up period completion | Change from baseline in SLEDAI-2K at 6 months and 24 months post-infusion. SLEDAI-2K is a validated global disease-activity index that quantifies SLE activity by rating the presence of 24 weighted clinical and laboratory descriptors across 9 organ systems (central nervous/visual, vascular, renal, musculoskeletal, cutaneous, mucosal/serosal, constitutional, and immunologic/hematologic) occurring within the prior 10 days. Each descriptor is credited only if attributable to active lupus (not infection, drug effect, metabolic cause, or unrelated comorbidity); descriptors are summed for a total score range 0-105, with higher scores indicating greater disease activity. |
| IMNM: Definition Of Improvement (DOI) | Throughout the first 24 months follow up period completion | Proportion of participants achieving DOI at 6 months post-infusion and during the study period |
| IMNM: Manual Muscle Test (MMT) | Throughout the first 24 months follow up period completion | Change from baseline in MMT at 6 months and 24 months post-infusion. MMT scale is a foundational, internationally recognized clinical tool for quantifying voluntary skeletal muscle strength in patients with neurologic and systemic diseases. |
| SSc: Revised Composite Response Index in Systemic Sclerosis (r-CRISS) | Throughout the first 24 months follow up period completion | Proportion of participants achieving r-CRISS at 6 months post-infusion and during the |
| SSc: modified Rodnan Skin Score (mRSS), FVC% | Throughout the first 24 months follow up period completion | Change from baseline in mRSS and FVC% at 6 months and 24 months post-infusion. mRSS is the international standard semi quantitative measure of skin thickening in SSc. Scores are summed for a total range of 0-51, with higher scores indicating greater skin involvement. |
| PK：Maximal plasma concentration (Cmax) | Throughout the first 24 months follow up period completion | Cmax of C-CAR168 in peripheral blood |
| PK: Time to reach the maximal plasma concentration (Tmax) | Throughout the first 24 months follow up period completion | Tmax of C-CAR168 in peripheral blood |
| PK: Duration in peripheral blood (Tlast) | Throughout the first 24 months follow up period completion | Tlast of C-CAR168 in peripheral blood |
| PK: Area under curve (AUC) | Throughout the first 24 months follow up period completion | AUC of C-CAR168 in peripheral blood |
| PD: Depletion of peripheral blood B cells, plasma cells, and CD20dim T cells | Throughout the first 24 months follow up period completion | — |
| PD: Decline of serum immunoglobulin | Throughout the first 24 months follow up period completion | — |
Countries
China
Contacts
CONTACTMin Liu, MD
CONTACTBin Liu, MD
Outcome results
None listed